Molecular Mechanisms of Dyslipidemias and Atherogenesis
Emphasizing receptor-mediated endocytic processes, we investigate molecular genetic, cell biological, and biochemical details of (i) the low density lipoprotein (LDL) receptor gene family in oocyte growth and embryo development, and of the receptor LR11 in smooth muscle cell biology, (ii) avian lipases and transfer proteins (i.e., the lipolytic proteome) of the granulosa cells surrounding the chicken oocyte as well as of the extraembryonic yolk sac, which mediate yolk lipid deposition and subsequent utilization by the embryo, respectively, (iii) the molecular genetic basis for human atherosclerosis caused by single-gene mutations that reduce or abolish receptor-mediated transport of lipoproteins and/or cholesterol, and (iv) the role of the recently discovered apolipoprotein, apo-AV, in the etiology of human pathological hypertriglyceridemia.
In regards to (i), we have elucidated the role of the LDLR family member LR11 in Ang-II stimulated vascular smooth muscle cell migration. A circulating soluble form of LR11, sLR11, is a novel marker of carotid IMT (intima-media thickness), and targeted disruption of the LR11 gene greatly reduces intimal thickening of arteries through attenuation of AngII-induced migration of SMCs (Ref. 1).
In the projects (ii) we have shown, for the first time in any system, that hepatic arylacetamide deacetylase (AADA), like the key lipase ATGL, is upregulated by fasting, and that its affinity for insoluble carboxylester substrates is compatible with an in vivo function similar to that of ATGL. Unknown heretofore, hepatic expression of chicken AADA is estrogen-responsive, and is induced to the same degree as the stimulation of hepatic VLDL-production by estrogen. These observations support the hypothesis that chicken ATGL, PNPLA3, and AADA play roles in acylglycerol metabolism related to the high rates of VLDL synthesis essential for reproduction (Ref. 2). We have characterized patatin-like phospholipases, and revealed their unique tissue distribution patterns in the laying hen.
In project (iv), we have achieved the first molecular and functional characterization of a nonmammalian ApoA-V, and have described novel mechanism for modulation of triglyceride levels by ApoA-V proposed based on discovery that the apo binds to LRs. Finally, we have established that a new chondroitin sulfate-modified collagen forms a follicular membrane which to date has been assumed to be a bona-fide basement membrane (Ref. 3).
Dr.rer.techn. (Techn. Univ. Vienna, 1975)
Habilitation 1986 (KFU Graz)
Professor, Dept. Biochemistry, University of Alberta, Edmonton, Canada 1989-1991
Professor and Chair, Dept. Molecular Genetics, University of Vienna; from 2004, Director of Dept. of Medical Biochemistry, Medical University of Vienna, 1991-2013
1982‐1985 Established Investigator of the American Heart Association
1985‐1990 Scholar of the Alberta Heritage Foundation for Medical Research
1990‐1992 Heritage Medical Scientist of the AHFMR and Scientist of the MRC Canada
1987 Gabor Szasz Prize of the German Society for Clinical Investigation
1987 Curt Adam Prize of the Soc. Continuing Edu. of Physicians, Germany
1988 Bristol Laboratories Senior Scientist Research Award
1991 Heinrich‐Wieland Preis
1987‐2007 22 Research Prizes to laboratory members
1997‐1999 Speaker, UniversityDepts. at the Vienna Biocenter
1999 Internatl. Advisory Board, Chiba University School Med., Japan
1996‐1999 Coordinator, Internatl. Ph.D.Program, Vienna Biocenter/University
2003‐2010 Coordinator, Dr. sci. med. Program “Molecular Biology in Medicine”
2007‐2010 President, Austrian Atherosclerosis Society
Plieschnig, Julia A; Gensberger, Eva T; Bajari, Tarek M; Schneider, Wolfgang J; Hermann, Marcela (2012). Renal LRP2 expression in man and chicken is estrogen-responsive. GENE;508(1):49-59. PMID: 22868208
Sakai, Shio; Nakaseko, Chiaki; Takeuchi, Masahiro; Ohwada, Chikako; Shimizu, Naomi; Tsukamoto, Shokichi; Kawaguchi, Takeharu; Jiang, Meizi; Sato, Yasunori; Ebinuma, Hiroyuki; Yokote, Koutaro; Iwama, Atsushi; Fukamachi, Isamu; Schneider, Wolfgang Johann; Saito, Yasushi; Bujo, Hideaki (2012). Circulating soluble LR11/SorLA levels are highly increased and ameliorated by chemotherapy in acute leukemias. Clinica chimica acta; international journal of clinical chemistry.;413(19-20):1542-8. PMID: 22750733
Bauer, Raimund; Plieschnig, Julia A; Finkes, Thomas; Riegler, Barbara; Hermann, Marcela; Schneider, Wolfgang J (2013). The developing chicken yolk sac acquires nutrient transport competence by an orchestrated differentiation process of its endodermal epithelial cells. J BIOL CHEM;2(288):1088-98. PMID: 23209291